Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections: a meta-analysis

World J Gastroenterol. 2012 Jun 28;18(24):3119-28. doi: 10.3748/wjg.v18.i24.3119.


Aim: To assess the rigorous relationship between human leukocyte antigens (HLA)-DR alleles and outcomes of hepatitis B virus (HBV) infections by means of meta-analysis.

Methods: Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Study quality was evaluated using the Newcastle-Ottawa Scale. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using Stata 11.0. Subgroup analyses were performed by ethnicity. Heterogeneity and publication bias analyses were performed to validate the credibility.

Results: A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included. Meta-analysis showed that HLA-DR*04 (OR = 0.72, 95% CI: 0.60-0.85) and DR*13 (OR = 0.27, 95% CI: 0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03 (OR = 1.47, 95% CI: 1.16-1.87) or DR*07 (OR = 1.59, 95% CI: 1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence. For the HLA-DR*01 polymorphism, a significantly association with HBV clearance was found in Chinese Han group (OR = 0.48, 95% CI: 0.26-0.86), but not found in other ethnic groups (P = 0.191). For other polymorphisms, no association with the HBV infection outcome was found.

Conclusion: HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLA-DR*03, and DR*07 alleles may be the risk factors for HBV persistence.

Keywords: Hepatitis B virus; Human leukocyte antigens; Meta-analysis; Polymorphism.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Asian People / genetics
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genotype
  • HLA-DR Antigens / genetics*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / epidemiology
  • Hepatitis B, Chronic / immunology
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Viral Load


  • Antiviral Agents
  • HLA-DR Antigens